Panel Urges End to Avastin Use in Breast Cancer

The 12 to 1 vote represents a stinging setback for Avastin, which is now the world’s best-selling cancer drug, with global sales of about $6 billion last year. The product has at times been hailed as a near miracle, the first medicine to work by blocking the flow of blood to tumors.

The data discussed at the meeting Tuesday suggested that, at least for advanced breast cancer, the initial data that led to approval was not borne out by subsequent studies.

“I’m really not seeing that this has a benefit for patients,” Natalie Compagni Portis, the patient representative on the committee, said during the meeting in Gaithersburg, Md. “Hope is very important, but to offer hope that isn’t substantiated I don’t think is responsible.”

Avastin, which is sold by Roche’s Genentech unit, will remain on the market even if the F.D.A. follows the committee’s advice, as it usually does. That is because Avastin is also permitted as a treatment for colon, lung, kidney and brain cancers. So even if the F.D.A. does indeed take the rare move of rescinding its approval, doctors would still be able to use Avastin off-label to treat breast cancer.

Insurers, however, might be reluctant to pay for an unapproved use. And breast cancer treatment would no longer be part of a program in which Genentech caps yearly spending on Avastin at $57,000 for patients with incomes below $100,000. Without the cap, the wholesale price of Avastin for a typical breast cancer patient would be $88,000, according to Genentech.

Avastin, also known as bevacizumab, is Roche’s best-selling product. Jeffery Holford, an analyst with Jefferies & Company, said Roche might now lose about $500 million of the estimated $700 million in Avastin sales to treat breast cancer in the United States. He predicted little effect in other countries because approvals there were not made on a conditional basis.

Genentech, in a statement, said it stood by the data and said that “Avastin should be an option for patients with this incurable disease.” Roche’s American depositary receipts fell $1.20, to close at $33 on Tuesday.

Avastin was given so-called accelerated approval in early 2008, a way for the F.D.A. to approve drugs for life-threatening diseases based on less than complete evidence of effectiveness. Manufacturers must then do further studies to confirm the benefit of the drug.

The two new trials sponsored by Roche for this purpose showed a much smaller effect of the drug, so small, that the committee voted 13-0 that the studies did not confirm the initial benefit.

In the initial study, use of Avastin delayed the worsening of patients’ disease by about 5.5 months. Those who received Avastin plus the chemotherapy drug paclitaxel went a median of 11.3 months before their tumors worsened, or progressed, compared to 5.8 months for those who got paclitaxel alone.

But use of Avastin did not prolong the women’s lives by a statistically significant amount, the gold standard for cancer drugs. And the drug had serious side effects for some patients.

The two new studies, in which different chemotherapy drugs were used with Avastin, showed even fewer signs that it could prolong lives. And the delay in a tumor worsening was much smaller. In one trial, it was just under a month and in the other about one to three months.

“It just delays by another visit before they get the news that their tumor progressed,” said Dr. Patrick Loehrer Sr., of Indiana University and a committee member.

Whether delayed worsening in tumors, a measure known as progression-free survival, is a valid goal for a cancer drug is controversial. Even patient groups were split when Avastin initially came up for approval for use in metastatic breast cancer.

Some said that only a reduction in symptoms or longer survival were meaningful to patients. Others said women worry less if the tumor is not worsening. They also argued that so many drugs were used by patients after the trial was over that any effect Avastin might have had in prolonging lives was washed out.

In December 2007, an F.D.A. advisory committee with some of the same members as Tuesday’s panel voted 5 to 4 against full approval. But in 2008, the F.D.A. granted accelerated approval.

On Tuesday, only one woman with breast cancer testified in favor of the drug, saying it had greatly improved her life and allowed her to golf again and go out with friends. Representatives of two patient groups urged the committee to vote for revocation.

For lung cancer and colon cancer, Avastin improved survival and got full approval. But in those cases as well, subsequent studies did not show as big a benefit as the initial studies.

Reversing the breast cancer approval would be a rare move for the F.D.A. A report by the Government Accountability Office last fall showed that none of the 90 drugs given accelerated approval had ever been removed from the market and that the agency sometimes did not make sure follow-up studies were done.

This June, however, the F.D.A. announced that Mylotarg, a little-used leukemia drug sold by Pfizer, would be withdrawn. In 2005, the agency heavily restricted use of the AstraZeneca lung cancer drug Iressa after it did not prolong survival in clinical trials.

But the Avastin studies were conducted promptly by Roche and evaluated by the F.D.A. “This is a good example of the system working,” said Dr. Wyndham Wilson of the National Cancer Institute, who served as chairman of the committee.

via nytimes.com

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